The long range goal of the proposed research is to further our understanding of the development and functioning of blood cells and how these processes are affected in particular disease states. The program focuses on red cells and lymphocytes in man, mice and chickens with particular concentration on the structure and function of the cell surface plasma membrane during differentiation and its role in maturation of the mature cell. A multidisciplinary approach, using the tools of biophysics, molecular biology, cell biology and biochemistry is employed. The five participants in the program are each experts in one or more of these areas. Project 1 (D. Engel) focuses on the intrinsic and extrinsic factors which result in hematopoietic stem cell propagation versus differentiation. Project 2 (V. Patel and D. Williams) closely parallels this project focusing on the role of adhesive interactions between bone marrow and stromal cells in development of multipotential hematopoietic stem cells. Project 3 (S. Pierce) studies lymphocyte development focusing on the biogenesis on antigen-derived cell surface interaction structures. Project 4 (R. MacDonald) addresses the molecular basis of the mechanical properties of the erythrocyte membrane. Project 5 (L. Lorand) focuses on the role of covalent modification of membrane skeletal proteins in the erythrocyte during differentiation. Key to the success of the overall effort are the collaborative interactions among participants which will allow technical as well as intellectual contributions to the individual projects. The interactions among the five participants in the program create a unique environment for collaboration between the participating graduate students and postdoctoral fellows specializing in biochemistry, molecular biology and cell biology of blood cells. Such a broadly based study, including gene regulation and the regulation of the assembly and function of essential cellular structures, will certainly bear fruit with regard to a better understanding of hematopoietic diseases and defective functions of mature cells.